A call for an end to calls for the end of invasion biology

Calls for the end of invasion biology are misguided. There is no evidence that modern invasion biology has progressed slowly in its short life. Although some aspects of biological invasions fit comfortably in the framework of ecological succession, many others do not. Some native species, particularly in the wake of various anthropogenic impacts, behave like invasive non‐native species, but the probability and degree of harmful impact are greater for non‐native than for native species. Neither native nor non‐native species suffer lack of attention and research by virtue of the fact that invasion biology focuses on the latter. Basing management solely on current observed impact is highly risky because impacts may be subtle but nonetheless important, and impacts often change, as they are contingent on the physical or biotic environment. The known harmful impacts of many non‐native species suggest that recent introductions warrant attention even if impacts are not evident. Neither is the focus of modern invasion biology on non‐native species motivated by xenophobia. Rather, it reflects the recognition of their likelihood of harmful impact. A related call for the end of traditional restoration ecology shares many features with calls to terminate invasion biology, not least because management of invasive non‐native species is a key component of restoration ecology. Such species are a dominant element in generating the ‘novel ecosystems’ that are said to render traditional restoration ecology obsolete. The argument that both invasion management and traditional restoration are largely futile endeavors is contradicted by substantial and growing successes in both fields.     

ATM limits incorrect end utilization during non-homologous end joining of multiple chromosome breaks

Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI-resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ.     

Capping one end of an actin filament affects elongation at the other end

The rates of elongation at the free ends of actin filaments were compared to those of intact filaments, when the one end was masked with muscle beta-actinin or cytochalasin D, using fixed actoheavy meromyosin and Limulus acrosomal actin bundles as seeds. Experimental conditions were chosen so as to prevent spontaneous filament formation as far as possible. The rate of elongation at the barbed end of fixed actoheavy meromyosin was reduced to about one-fourth when the other pointed end was capped by beta-actinin, and that at the pointed end was reduced to one-third when the barbed end was blocked by cytochalasin D. Similar effects were also observed with the packed actin bundles of horseshoe crab sperm, although the decreases in elongation were less marked: 50-60% of the control both in the presence of beta-actinin and cytochalasin D. To explain the peculiar "end effect" described above, it is proposed that possible conformational changes at one end of an actin filament caused by the binding of a capping substance are transmitted successively to the other end so as to affect the elongation there.     

The end of the road

After some 60 years in research, a few months before my final retirement (there were a few temporary ones), the time has come to reminisce.     

The end of the road

After some 60 years in research, a few months before my final retirement (there were a few temporary ones), the time has come to reminisce.     

Non-homologous end joining often uses microhomology: Implications for alternative end joining

Artemis and PALF (also called APLF) appear to be among the primary nucleases involved in non-homologous end joining (NHEJ) and responsible for most nucleolytic end processing in NHEJ. About 60% of NHEJ events show an alignment of the DNA ends that use 1 or 2 bp of microhomology (MH) between the two DNA termini. Thus, MH is a common feature of NHEJ. For most naturally occurring human chromosomal deletions (e.g., after oxidative damage or radiation) and translocations, such as those seen in human neoplasms and as well as inherited chromosomal structural variations, MH usage occurs at a frequency that is typical of NHEJ, and does not suggest major involvement of alternative pathways that require more extensive MH. Though we mainly focus on human NHEJ at double-strand breaks, comparison on these points to other eukaryotes, primarily S. cerevisiae, is informative.     

When will it ever end? When will it ever end?

When will COVID‐19 ever end? Various countries employ different strategies to address this; time will tell what the best response was. Subject Categories: S&S: Economics & Business, Microbiology, Virology & Host Pathogen Interaction, S&S: Ethics

Peter Seeger’s anti‐war song with its poignant refrain, stretching out the second “ever” to convey hopeless fatigue with the continuing loss of life, applies to the pandemic too. “Where have all the old folks gone?” may replace the loss of young men in Seeger’s song. But they keep going, and it is not happening on distant continents; it is happening with them distanced in places they called home. At the time of writing in early March, there are a few answers to Seeger’s question from around the world. There are the isolationists who say that maintaining a tight cordon around a COVID‐free zone is the way to get out of the pandemic. There are the optimists with undiluted faith in the vaccines who say it will be all over when everyone will get a jab. And there are the fatalists who say it will eventually end when herd immunity stops the pandemic after many people have died or fallen ill.Living in Australia where there are only sporadic cases of COVID, it is tempting to see the merits of the isolationist strategy. Only a small number of international travelers can enter the continent every week. Coming back from Europe in November, arrival at Brisbane airport was followed by police‐cordoned transfer to a pre‐allocated hotel—no choice, no balcony, no open windows—where we stayed (and paid) for a 14‐day confinement. On release, it was strange to find that life was close to normal: no masks and nearly no restrictions for public and private meetings. Sporting events and concerts do not have attendance restrictions. All that was different were easy‐to‐follow rules about social distancing in shops or on the streets, limited numbers of people on lifts, and a requirement to register when going to a restaurant or bar.Since I settled back to COVID‐free life in Australia, the last incident in Queensland occurred a month ago when a cleaner at a quarantined hotel got infected. It was “treated” with an instant 3‐day “circuit‐breaker” lockdown for the whole community. Forensic contact tracing was easy, and large numbers of people lined up for testing. Seven days later, the outbreak was declared over. A police inquiry examined the case to see whether regulations needed to be changed. The same rapid and uncompromising lockdown protocols have been employed in Melbourne, Perth, or New Zealand whenever somebody in the community tested positive. There is also continuous monitoring of public wastewater for viral RNA to quickly identify any new outbreak. Small numbers of positive cases are treated with maximum restrictions until life can return to “normal”. The plan is to expand these state policies to achieve a COVID‐free in Australia along with New Zealand and eventually the Pacific Islands.The strict isolationist policy has its downsides. Only Australian citizens or permanent residents are allowed to enter the country. Families have been separated for months. Sudden closing of borders makes the country play some musical chair game: When the whistle is blown, you stay where you are. Freedoms that have been considered as human rights have been side‐stepped. Government control is overt. Nonetheless, the dominant mood is that the good of the community trumps that the individual rights, which may come as a surprise in a liberal democratic society. People benefit from the quality of (local) life, and while there is an economic hiatus for tourism and international student business, the overall economy will come out without too much damage. Interestingly, the most draconian State leaders get the highest rating in the polls and elections. Clear, unwavering leadership is appreciated.Given their geographical situation, Australia, New Zealand, and other islands have clear advantages in pursuing their successful isolationist policies. For most of the rest of the world though, the answer to “when will it ever end” points resolutely and confidently to vaccines. With amazing speed and fantastic efforts, scientists in university and industry laboratories all over the world developed these silver bullets, the Krypton that will put the virus in its place. Most countries have now placed all their chips on the vaccine square of the roulette table.However, there are some aspects to consider before COVID will raise the white flag. It will take months to achieve herd immunity; a long time during which deaths, illness, and restrictions will continue. With different vaccines in production and use, it is likely that some will protect better against the virus than others. The duration of their protection is still unclear, and hence, the vaccine roll‐out could be interminable. More SARS‐CoV‐2 variants are on the rise challenging the long‐term efficacy of the vaccine(s). The logistics and production demands are significant and will become even more acute as the vaccines go to developing countries. Anti‐vaxxers already see this as an opportunity to spread their mixture of lies, exaggerations, and selective information, which may make it more difficult to inoculate sufficient numbers in some communities. And yet, for most countries, there is no real alternative to breaking the vicious cycle of persistent local infections that are slowed by restrictions only to explode again when Christmas or business or the public mood demands a break. The optimists are realists in this scenario.The third cohort are the fatalists. The Spanish flu ended after two years, and 50 million deaths and COVID will also run out of susceptible targets in due course. But herd immunity is a crude concept when the herd is people: our families, friends, and neighbors. Fatalism could translate into doing nothing and let people die and that is not a great policy when facing disaster.The alternative of doing nothing is to combine various strategies as Israel and the UK are doing: to adopt some of the isolationist approaches while vaccinating as many people as quickly as possible. The epidemiological data indeed show that restrictions on interactions do reduce the number of cases. Some countries, Ireland for example, have seen ten‐fold reductions in daily cases even before the first needle hit an arm following tightening of social interactions. This shows that the real impact of the vaccination will only be known when a sufficient percentage of the population has been immunized and the social restrictions are lifted. Australia with its significant travel restrictions is another successful example. In addition, contact tracing and testing are very helpful to contain outbreaks and create corona‐free zones that can be expanded in a controlled manner. Of course, there are local, political, and economic factors at play, but these should not block attempts to lower infection rates until sufficient numbers of vaccine doses become available.So, the answer to the question “when will it ever end?” will require a combination of the isolationists and the optimists such that the fatalist solution does not prevail. It will be interesting to revisit this question in two years’ time to see what the correct answer turns out to be.     

Non-homologous DNA end joining

DNA double strand breaks (DSB) are the most serious form of DNA damage. Repair of DSBs is important to prevent chromosomal fragmentation, translocations and deletions. Non-homologous end joining (NHEJ) is one of three major pathways for the repair of DSBs in human cells. In this process two DNA ends are joined directly, usually with no sequence homology, although in the case of same polarity of the single stranded overhangs in DSBs, regions of microhomology are utilized. NHEJ is typically imprecise, a characteristic that is useful for immune diversification in lymphocytes in V(D)J recombination. The main components of the NHEJ system in eukaryotes are the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku proteins, XRCC4, DNA ligase IV, and Artemis. This review focuses on the mechanisms an dregulation of DSB repair by NHEJ in mammalian cells.